Inflammation, immunity, and vascular remodeling in pulmonary hypertension; Evidence for complement involvement?
Journal
Global cardiology science & practice
ISSN: 2305-7823
Titre abrégé: Glob Cardiol Sci Pract
Pays: Qatar
ID NLM: 101613130
Informations de publication
Date de publication:
30 Apr 2020
30 Apr 2020
Historique:
entrez:
2
6
2020
pubmed:
2
6
2020
medline:
2
6
2020
Statut:
epublish
Résumé
Pulmonary (arterial) hypertension (PH/PAH) is a life-threatening cardiopulmonary disorder. Experimental evidence suggests involvement of inflammatory and autoimmune processes in pathogenesis of PH/PAH, however the triggering and disease-promoting mechanisms remain unknown. The complement system is a key arm of innate immunity implicated in various pro-inflammatory and autoimmune diseases, yet, surprisingly little is known about the role of complement in PH/PAH pathogenesis. The preponderance of the existing data associates complement with PH/PAH via analysis of plasma and does not study the lung directly. Therefore, we aimed to resolve this by analyzing both the mechanisms of local lung-specific complement activation and the correlation of dysregulated plasma complement to clinical outcome in PAH patients. In our recent studies, reviewed herein, we show, for the first time, that immunoglobulin-driven activation of the complement cascade, specifically its alternative pathway, in the pulmonary perivascular areas, is a key mechanism initiating pro-inflammatory processes in the early stage of experimental hypoxic PH (a form of "sterile inflammation"). In human patients with end-stage PAH, we have demonstrated that perivascular deposition of immunoglobulin G (IgG) and activation of the complement cascade are "longitudinally" persistent in the disease. We also showed, using unbiased network analysis, that plasma complement signaling, including again the Alternative pathway, is a prognostic factor of survival in patients with idiopathic PAH (IPAH). Based on these initial findings, we suggest that vascular-specific, immunoglobulin-driven dysregulated complement signaling triggers and maintains pulmonary vascular remodeling and PH. Future experiments in this area would facilitate discoveries on whether complement signaling can serve both as a biomarker and therapeutic target in PH/PAH.
Identifiants
pubmed: 32478115
doi: 10.21542/gcsp.2020.1
pii: gcsp.2020.1
pmc: PMC7232865
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
e202001Subventions
Organisme : NIH HHS
ID : S10 OD021641
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL014985
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL152961
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK113586
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK076690
Pays : United States
Informations de copyright
Copyright ©2020 The Author(s).
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